A genome-wide association study of seasonal pattern mania identifies NF1A as a possible susceptibility gene for bipolar disorder

J Affect Disord. 2013 Feb 20;145(2):200-7. doi: 10.1016/j.jad.2012.07.032. Epub 2012 Aug 25.


Objective: The use of subphenotypes may be an effective approach for genetic studies of complex diseases. Manic episodes with a seasonal pattern may distinguish phenotypic subgroups of bipolar subjects that may also differ genetically.

Method: We have performed a genome-wide association study using GAIN genotype data from the Bipolar Genome Study (BiGS) and bipolar subjects that were categorized as having either seasonal or non-seasonal patterned manic episodes.

Results: A bipolar case-only analysis identified three genomic regions that differed between seasonal and non-seasonal patterned manic episodes of bipolar subjects. The most significant association was for rs41350144, which lies within an intron of NF1A gene on 1p31 (P=3.08×10(-7), OR=2.27). Haplotype construction using flanking three SNPs (rs41453448, rs1125777, and rs12568010) spanning 7549bp showed a more significant association (P=2.12×10(-7), OR=0.4).

Conclusions: These data suggest that genetic variants in the NF1A gene region may predispose to seasonal patterned of mania in bipolar disorder.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bipolar Disorder / genetics*
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Genotype
  • Haplotypes
  • Humans
  • Introns / genetics
  • NFI Transcription Factors / genetics*
  • Polymorphism, Single Nucleotide
  • Seasons*


  • NFI Transcription Factors
  • NFIA protein, human